Induction of LTP

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Figure 10–7. Activation of NMDA receptors, modulated by other ionotropic amino acid receptors, triggers the induction of LTP in principal cells of area CA1 and dentate gyrus. A. Low-frequency stimulation of Schaffer commissural axons evokes an EPSP that is mediated by L-glutamate acting on AMPA receptors. The EPSP is followed by a biphasic IPSP, produced by glutamatergic excitation of feedforward GABAergic interneurons. The early part of the IPSP is due to activation of GABAA receptors, which are permeable to Clions; the slow component of the IPSP reflects activation of GABAB receptors, indirectly coupled to K channels. Because of its slow kinetics and the voltage-dependent block of its channel by Mg2 ions, the NMDA receptor contributes little to the EPSP at low frequencies of stimulation. B. During high-frequency stimulation, the activated spines become strongly depolarized with the result that the Mg2 block of the NMDA receptor channel is relieved, allowing Ca2 to permeate through the receptor. Factors that contribute to sustained depolarization, including temporal summation of EPSPs and the accumulation of Cl- in the spine and K in the synaptic cleft, leading to depolarizing shifts in reversal potentials. Some protocols, in particular theta burst stimulation, depend for their efficacy on the suppression of inhibition mediated via GABAB autoreceptors on inhibitory terminals. The suppression of GABA release reaches a maximum around 200 ms after a priming stimulus, explaining the peculiar efficacy of priming and theta burst stimulation (see text). (Source: After Bliss and Collingridge (1993).

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